Objectives: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). Patients and methods: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100mg once daily (qd) or 100mg twice daily (bid) to compare with moxifloxacin tablets 400mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). Results: A total of 343 patients were randomized (sitafloxacin 100mg qd, n=117, sitafloxacin 100mg bid, n=116, moxifloxacin, n=110), 291 patients were included in PPS (sitafloxacin 100mg qd, n=96, sitafloxacin 100mg bid, n=94, moxifloxacin, n=101). The clinical cure rate was 94.8% in sitafloxacin 100mg qd group, 96.8% in sitafloxacin 100mg bid group, and 95.0% in moxifloxacin group. At TOC visit, the microbiological success rate was 97.0% (32/33) in sitafloxacin 100mg qd group, 97.1% (34/35) in sitafloxacin 100mg bid group, and 94.9% (37/39) in moxifloxacin group in microbiological evaluable set (MES). The incidence of study drug-related adverse events (AEs) was 23.3% (27/116) in sitafloxacin 100mg qd group, 29.8% (34/114) in sitafloxacin 100mg bid group, and 28.2% (31/110) in moxifloxacin group (P> 0.05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased A c c e p t e d M a n u s c r i p t platelet count, and ALT elevation. All the AEs resolved completely after discontinuation of study drug. Conclusion: Sitafloxacin 100mg qd or 100mg bid for 7-10 days is not inferior to moxifloxacin 400mg qd for 7-10 days in the clinical efficacy for adult CAP patients. Sitafloxacin provides safety profile comparable to moxifloxacin.